Induction of direct antimicrobial activity through mammalian toll-like receptors

The mammalian innate immune system retains from Drosophila a family of homo logous Toll-like receptors (TLRs) that mediate responses to microbial ligan ds. Here, we show that TLR2 activation Leads to killing of intracellular My cobacterium tuberculosis in both mouse and human macrophages, through disti nct mechanisms. In mouse macrophages, bacterial lipoprotein activation of T LR2 Leads to a nitric oxide-dependent killing of intracellular tubercle bac illi, but in human monocytes and alveolar macrophages, this pathway was nit ric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll rec eptors do) to microbial ligands and also have the ability to activate antim icrobial effector pathways at the site of infection.